Evidence map›Paper›PMID 36209796›Full record

ArticleGastroenterology2023

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

Alessandro Paniccia, Patricio M Polanco, Brian A Boone, Abigail I Wald, Kevin McGrath, Randall E Brand, Asif Khalid, Nisa Kubiliun, Anne Marie O'Broin-Lennon, Walter G Park and 58 more

Open access · bronzeAbstract read
In one paragraph

Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
16.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 167 citations in OpenAlex.

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  12. Cytology andJournal of clinical medicine · 2026
    Article
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  16. Cystic neoplasms of pancreas.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2026
    Review
  17. Article
  18. Review
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  20. Article

34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

68 authors at 15 institutions in 2 countries.

Alessandro PanicciaDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Patricio M PolancoDepartment of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas.
Brian A BooneDepartment of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia.
Abigail I WaldDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Kevin McGrathDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Randall E BrandDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Asif KhalidDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
Nisa KubiliunDepartment of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Anne Marie O'Broin-LennonThe Sol Goldman Pancreatic Cancer Research Center, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Walter G ParkDepartment of Medicine, Stanford University, Stanford, California.
Jason KlapmanDepartment of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida.
Benjamin TharianDepartment of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Sumant InamdarDepartment of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Kenneth FasanellaDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
John NasrDepartment of Medicine, Wheeling Hospital, West Virginia University Health Sciences Center, Morgantown, West Virginia.
Jennifer ChennatDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Rohit DasDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
John DeWittDepartment of Gastroenterology and Hepatology, Indiana University Health Medical Center, Indianapolis, Indiana.
Jeffrey J EaslerDepartment of Gastroenterology and Hepatology, Indiana University Health Medical Center, Indianapolis, Indiana.
Benjamin BickDepartment of Gastroenterology and Hepatology, Indiana University Health Medical Center, Indianapolis, Indiana.
Harkirat SinghDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Kimberly J FairleyDepartment of Medicine, Section of Gastroenterology & Hepatology, West Virginia University Health Sciences Center, Morgantown, West Virginia.
Savreet SarkariaDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Tarek SawasDepartment of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Wasseem SkefDepartment of Medicine, Division of Gastroenterology and Hepatology, Loma Linda University Medical Center, Loma Linda, California.
Adam SlivkaDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Anna TavakkoliDepartment of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Shyam ThakkarDepartment of Medicine, Section of Gastroenterology & Hepatology, West Virginia University Health Sciences Center, Morgantown, West Virginia.
Victoria KimDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Hendrikus Dutch VanderveldtDepartment of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Allyson RichardsonDepartment of Medicine, Stanford University, Stanford, California.
Michael B WallaceDepartment of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida; Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
Bhaumik BrahmbhattDepartment of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
Megan EngelsDepartment of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
Charles GabbertDepartment of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Mohannad DugumDigestive Health Center, Essentia Health-Duluth Clinic, Duluth, Minnesota.
Samer El-DikaDepartment of Medicine, Stanford University, Stanford, California.
Yasser BhatDepartment of Gastroenterology, Palo Alto Medical Foundation (PAMF), Mountain View, California.
Sanjay RamrakhianiDepartment of Gastroenterology, Palo Alto Medical Foundation (PAMF), Mountain View, California.
Gennadiy BakisPortland Gastroenterology Center, Portland, Maine.
Daniil RolshudPortland Gastroenterology Center, Portland, Maine.
Gordon MillspaughPortland Gastroenterology Center, Portland, Maine.
Thomas TiellemanDepartment of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Carl SchmidtDepartment of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia.
John MansourDepartment of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas.
Wallis MarshDepartment of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia.
Melanie OngchinDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Barbara CentenoDepartment of Pathology, Moffitt Cancer Center, Tampa, Florida.
Sara E MonacoDepartment of Pathology, Geisinger Medical Center, Danville, Pennsylvania.
N Paul OhoriDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Sigfred LajaraDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Elizabeth D ThompsonThe Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Ralph H HrubanThe Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Phoenix D BellDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Katelyn SmithDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Jennifer B PermuthDepartment of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida.
Christopher VandenbusscheThe Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Wayne ErnstDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Maria GrupilloDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Cihan KayaDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Melissa HoggDepartment of Surgery, NorthShore University Health System, Chicago, Illinois.
Jin HeThe Sol Goldman Pancreatic Cancer Research Center, Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Christopher L WolfgangThe Sol Goldman Pancreatic Cancer Research Center, Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Surgery, NYU Langone Health, New York, New York.
Kenneth K LeeDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Herbert ZehDepartment of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas.
Amer ZureikatDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Marina N NikiforovaDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: nikiforovamn@upmc.edu.
Aatur D SinghiDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: singhiad@upmc.edu.
University of Pittsburgh Medical Center · USThe University of Texas Southwestern Medical Center · USJohns Hopkins University · USWest Virginia University · USIndiana University Health · USJacksonville College · USMoffitt Cancer Center · USStanford University · USUniversity of Arkansas for Medical Sciences · USEssentia Health · USGeisinger Medical Center · USLoma Linda University Medical Center · USNorthShore University HealthSystem · USUPMC Health System · USVA Pittsburgh Healthcare System · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI JAFFEE, ELIZABETH M. · 1993 to 2022
$54.6M
Validation of biomarkers for risk prediction and early diagnosis of Pancreatic AdenocarcinomaU01CA200466 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Surinder K. Batra, Randall Brand · 2016 to 2026
$11.3M
Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9M
The Prognostic Significance and Mechanistic Determination of Chromatin Remodeling Biomarkers in Non-Functional Pancreatic Neuroendocrine TumorR37CA263622 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Aatur Dilip Singhi · 2021 to 2026
$3.4M
NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA062924NCI NIH HHS R37 CA263622NCI NIH HHS U01 CA200466NIDDK NIH HHS P30 DK120531
6 · The paper itself

Abstract

BACKGROUND &

aimsNext-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time.

methodsThe performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens.

resultsAmong 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations.

conclusionsPancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Indexed as

Cystadenoma, SerousPancreatic CystPancreatic NeoplasmsEndoscopic Ultrasound-Guided Fine Needle AspirationGenomicsHigh-Throughput Nucleotide SequencingHumansMitogen-Activated Protein KinasesProspective StudiesRetrospective StudiesMitogen-Activated Protein KinasesDiagnosisEarly DetectionPancreasPancreatic CancerPancreatic Neoplasm

Identifiers

PMID36209796
PMCPMC9844531
OpenAlexW4302306679

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.